Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

156INTRODUCTION: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. METHODS: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan-Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. RESULTS: About 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC-based triple-therapies, aHR = 3.56, p = 0.012 for tenofovir-based) and for toxicity (aHR = 5.26, p = 0.030 for ABC-based, aHR = 6.60, p = 0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. CONCLUSIONS: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practicenonenoneMondi A.; Cozzi-Lepri A.; Tavelli A.; Rusconi S.; Vichi F.; Ceccherini-Silberstein F.; Calcagno A.; De Luca A.; Maggiolo F.; Marchetti G.; Antinori A.; d'Arminio Monforte A.; Andreoni M.; Castagna A.; Castelli F.; Cauda R.; Di Perri G.; Galli M.; Iardino R.; Ippolito G.; azzarin A.; Rezza G.; von Schloesser F.; Viale P.; Ceccherini-Silberstein F.; Cozzi-Lepri A.; Girardi E.; Lo Caputo S.; Mussini C.; Puoti M.; Perno C.F.; Balotta C.; Bandera A.; Bonora S.; Borderi M.; Capetti A.; Capobianchi M.R.; Cicalini S.; Cingolani A.; Cinque P.; Di Biagio A.; Gianotti N.; Gori A.; Guaraldi G.; Lapadula G.; Lichtner M.; Madeddu G.; Maggiolo F.; Monno L.; Nozza S.; Quiros Roldan E.; Rossotti R.; Rusconi S.; Santoro M.M.; aracino A.; Sarmati L.; Fanti I.; Galli L.; Lorenzini P.; Rodano' A.; Macchia M.; Tavelli A.; Carletti F.; Carrara S.; Di Caro A.; Graziano S.; Petrone F.; Prota G.; Quartu S.; Truffa S.; Giacometti I.A.; Costantini A.; Barocci V.; Angarano G.; Fabrizio C.; Suardi C.; i V.; Verucchi G.; Castelnuovo F.; Minardi C.; Menzaghi B.; Abeli C.; Cacopardo B.; Celesia B.; Vecchiet J.; Falasca K.; Pan A.; Lorenzotti S.; Sighinolfi L.; Segala D.; Blanc P.; Cassola G.; Viscoli C.; lessandrini A.; Bobbio N.; Mazzarello G.; Pozzetto I.; Bonfanti P.; Molteni C.; Chiodera A.; Milini P.; Nunnari G.; Pellicano G.; Rizzardini G.; Bai F.; Moioli M.C.; Piolini R.; Ridolfo A.L.; Salpietro S.; Tincati C.; Puzzolante C.; Migliorino C.; Sangiovanni V.; Borgia G.; Esposito V.; Di Martino F.; Gentile I.; Maddaloni L.; Cattelan A.M.; Marinello S.; Cascio A.; Colomba C.; Baldelli F.; Schiaroli E.; Parruti G.; Sozio F.; Magnani G.; Ursitti M.A.; Cristaudo A.; Vullo V.; Acinapura R.; Baldin G.; Capozzi M.; Rivano Capparucia M.; Iaiani G.; atini A.; Mastrorosa I.; Plazzi M.M.; Savinelli S.; Vergori A.; Cecchetto M.; Viviani F.; Bagella P.; Rossetti B.; Fontana Del Vecchio R.; Francisci D.; Di Giuli C.; Caramello P.; Orofino G.C.; Sciandra M.; Bassetti M.; ondero A.; Pellizzer G.; Manfrin V.; Starnini G.; alungo A.Mondi, A.; Cozzi-Lepri, A.; Tavelli, A.; Rusconi, S.; Vichi, F.; Ceccherini-Silberstein, F.; Calcagno, A.; De Luca, A.; Maggiolo, F.; Marchetti, G.; Antinori, A.; d'Arminio Monforte, A.; Andreoni, M.; Castagna, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Azzarin, A.; Rezza, G.; von Schloesser, F.; Viale, P.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Perno, C. F.; Balotta, C.; Bandera, A.; Bonora, S.; Borderi, M.; Capetti, A.; Capobianchi, M. R.; Cicalini, S.; Cingolani, A.; Cinque, P.; Di Biagio, A.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Madeddu, G.; Maggiolo, F.; Monno, L.; Nozza, S.; Quiros Roldan, E.; Rossotti, R.; Rusconi, S.; Santoro, M. M.; Aracino, A.; Sarmati, L.; Fanti, I.; Galli, L.; Lorenzini, P.; Rodano', A.; Macchia, M.; Tavelli, A.; Carletti, F.; Carrara, S.; Di Caro, A.; Graziano, S.; Petrone, F.; Prota, G.; Quartu, S.; Truffa, S.; Giacometti, I. A.; Costantini, A.; Barocci, V.; Angarano, G.; Fabrizio, C.; Suardi, C.; I, V.; Verucchi, G.; Castelnuovo, F.; Minardi, C.; Menzaghi, B.; Abeli, C.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Pan, A.; Lorenzotti, S.; Sighinolfi, L.; Segala, D.; Blanc, P.; Cassola, G.; Viscoli, C.; Lessandrini, A.; Bobbio, N.; Mazzarello, G.; Pozzetto, I.; Bonfanti, P.; Molteni, C.; Chiodera, A.; Milini, P.; Nunnari, G.; Pellicano, G.; Rizzardini, G.; Bai, F.; Moioli, M. C.; Piolini, R.; Ridolfo, A. L.; Salpietro, S.; Tincati, C.; Puzzolante, C.; Migliorino, C.; Sangiovanni, V.; Borgia, G.; Esposito, V.; Di Martino, F.; Gentile, I.; Maddaloni, L.; Cattelan, A. M.; Marinello, S.; Cascio, A.; Colomba, C.; Baldelli, F.; Schiaroli, E.; Parruti, G.; Sozio, F.; Magnani, G.; Ursitti, M. A.; Cristaudo, A.; Vullo, V.; Acinapura, R.; Baldin, G.; Capozzi, M.; Rivano Capparucia, M.; Iaiani, G.; Atini, A.; Mastrorosa, I.; Plazzi, M. M.; Savinelli, S.; Vergori, A.; Cecchetto, M.; Viviani, F.; Bagella, P.; Rossetti, B.; Fontana Del Vecchio, R.; Francisci, D.; Di Giuli, C.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Ondero, A.; Pellizzer, G.; Manfrin, V.; Starnini, G.; Alungo, A

Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-na\uefve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Na\uefve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan\u2013Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results: About 1679 individuals (932 ART-na\uefve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-na\uefve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-na\uefve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-na\uefve (2.1%) and TE (1.7%) patients. In ART-na\uefve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC-based triple-therapies, aHR = 3.56, p = 0.012 for tenofovir-based) and for toxicity (aHR = 5.26, p = 0.030 for ABC-based, aHR = 6.60, p = 0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART na\uefve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-na\uefve as well as in treated individuals reassures on the use of DTG in everyday clinical practice

Durability of first-line regimens including integrase strand transfer inhibitors ({INSTIs}): data from a real-life setting

Objectives: To evaluate the durability of three integrase strand transfer inhibitors (INSTIs) and two NRTIs in ART-naive individuals.Methods: The study design was observational. Patients were HIV-positive, ART-naive subjects starting raltegravir, elvitegravir/cobicistat or dolutegravir with two NRTIs. The primary endpoint was time to treatment failure, i.e. occurrence of virological failure (first of two consecutive plasma HIV RNAs >= 200 copies/mL after 24 weeks) or INSTI discontinuation for any reason apart from simplification. Secondary endpoints were INSTI discontinuation due to toxicity/intolerance and CD4 count response. Survival analysis was done using Kaplan-Meier and Cox regression.Results: Two thousand and sixteen patients were included: 310 (15.4%) started raltegravir-based regimens, 994 (49.3%) started dolutegravir-based regimens and 712 (35.3%) started elvitegravir/cobicistat-based regimens. Over a median of 11months, 167 patients experienced treatment failure; the 1 year probability of treatment failure was 6.5% for raltegravir, 5.4% for dolutegravir and 6.7% for elvitegravir/cobicistat (P = 0.001). Sixty-eight patients (3.4%) discontinued INSTIs owing to toxicity/intolerance. By multivariable analysis, patients starting raltegravir had a 2.03-fold (95% CI = 1.2-3.2) higher risk and patients on elvitegravir/cobicistat a 1.88-fold (95% CI = 1.2-2.9) higher risk of treatment failure versus dolutegravir; there was no difference in risk of discontinuation due to toxicity/intolerance when comparing dolutegravir and raltegravir and marginal evidence for a difference when comparing elvitegravir/cobicistat and dolutegravir (adjusted relative hazard = 1.94 for elvitegravir/cobicistat versus dolutegravir, 95% CI = 1.00-3.76, P = 0.05).Conclusions: In our real-life setting, INSTI-based regimens showed high potency and durability. Among regimens currently recommended in Europe, those including dolutegravir are associated with a lower risk of treatment failure

Durability of first-line regimens including integrase strand transfer inhibitors (INSTIs): data from a real-life setting

To evaluate the durability of three integrase strand transfer inhibitors (INSTIs) and two NRTIs in ART-naive individuals